False positive reduction in CADe using diffusing scale space

Segmentation is typically the first step in computer-aided-detection (CADe). The second step is false positive reduction which usually involves computing a large number of features with thresholds set by training over excessive data set. The number of false positives can, in principle, be reduced by extensive noise removal and other forms of image enhancement prior to segmentation. However, this can drastically affect the true positive results and their boundaries. We present a post-segmentation method to reduce the number of false positives by using a diffusion scale space. The method is illustrated using Integral Invariant scale space, though this is not a requirement. It is quite general, does not require any prior information, is fast and easy to compute, and gives very encouraging results. Experiments are performed both on intensity mammograms as well as on Volpara® density maps

Searching for Far-Ultraviolet Auroral/Dayglow Emission from HD209458b

We present recent observations from the HST-Cosmic Origins Spectrograph aimed at characterizing the auroral emission from the extrasolar planet HD209458b. We obtained medium-resolution (R~18-20,000) far-ultraviolet (1150-1700A) spectra at both the Phase 0.25 and Phase 0.75 quadrature positions as well as a stellar baseline measurement at secondary eclipse. This analysis includes a catalog of stellar emission lines and a star-subtracted spectrum of the planet. We present an emission model for planetary H2 emission, and compare this model to the planetary spectrum. No unambiguously identifiable atomic or molecular features are detected, and upper limits are presented for auroral/dayglow line strengths. An orbital velocity cross-correlation analysis finds a statistically significant (3.8 sigma) feature at +15 (+/- 20) km/s in the rest frame of the planet, at 1582 A. This feature is consistent with emission from H2 B-X (2-9) P(4) (lambda_{rest} = 1581.11 A), however the physical mechanism required to excite this transition is unclear. We compare limits on relative line strengths seen in the exoplanet spectrum with models of ultraviolet fluorescence to constrain the atmospheric column density of neutral hydrogen between the star and the planetary surface. These results support models of short period extrasolar giant planets with weak magnetic fields and extended atomic atmospheres.Comment: Accepted to ApJ. 12 pages, 5 figures, 4 table

Studies of Single-Molecule Dynamics in Microorganisms

Fluorescence microscopy is one of the most extensively used techniques in the life sciences. Considering the non-invasive sample preparation, enabling live-cell compliant imaging, and the specific fluorescence labeling, allowing for a specific visualization of virtually any cellular compound, it is possible to localize even a single molecule in living cells. This makes modern fluorescence microscopy a powerful toolbox. In the recent decades, the development of new, "super-resolution" fluorescence microscopy techniques, which surpass the diffraction limit, revolutionized the field. Single-Molecule Localization Microscopy (SMLM) is a class of super-resolution microscopy methods and it enables resolution of down to tens of nanometers. SMLM methods like Photoactivated Localization Microscopy (PALM), (direct) Stochastic Optical Reconstruction Microscopy ((d)STORM), Ground-State Depletion followed by Individual Molecule Return (GSDIM) and Point Accumulation for Imaging in Nanoscale Topography (PAINT) have allowed to investigate both, the intracellular spatial organization of proteins and to observe their real-time dynamics at the single-molecule level in live cells. The focus of this thesis was the development of novel tools and strategies for live-cell SingleParticle Tracking PALM (sptPALM) imaging and implementing them for biological research. In the first part of this thesis, I describe the development of new Photoconvertible Fluorescent Proteins (pcFPs) which are optimized for sptPALM lowering the phototoxic damage caused by the imaging procedure. Furthermore, we show that we can utilize them together with Photoactivatable Fluorescent Proteins (paFPs) to enable multi-target labeling and read-out in a single color channel, which significantly simplifies the sample preparation and imaging routines as well as data analysis of multi-color PALM imaging of live cells. In parallel to developing new fluorescent proteins, I developed a high throughput data analysis pipeline. I have implemented this pipeline in my second project, described in the second part of this thesis, where I have investigated the protein organization and dynamics of the CRISPR-Cas antiviral defense mechanism of bacteria in vivo at a high spatiotemporal level with the sptPALM approach. I was successful to show the differences in the target search dynamics of the CRISPR effector complexes as well as of single Cas proteins for different target complementarities. I have also first data describing longer-lasting bound-times between effector complex and their potential targets in vivo, for which only in vitro data has been available till today. In summary, this thesis is a significant contribution for both, the advances of current sptPALM imaging methods, as well as for the understanding of the native behavior of CRISPR-Cas systems in vivo

Investigation of electrical conductivity in amorphous semiconductors Final report

Theoretical and numerical model study of oxidation kinetics based on ionic diffusion in discrete lattice

Characterising pattern asymmetry in pigmented skin lesions

Abstract. In clinical diagnosis of pigmented skin lesions asymmetric pigmentation is often indicative of melanoma. This paper describes a method and measures for characterizing lesion symmetry. The estimate of mirror symmetry is computed first for a number of axes at different degrees of rotation with respect to the lesion centre. The statistics of these estimates are the used to assess the overall symmetry. The method is applied to three different lesion representations showing the overall pigmentation, the pigmentation pattern, and the pattern of dermal melanin. The best measure is a 100% sensitive and 96% specific indicator of melanoma on a test set of 33 lesions, with a separate training set consisting of 66 lesions

The importance of organic phosphorus sources, transfers and impacts across the agricultural continuum

This thesis investigates the risks posed by organic phosphorus (P) from agriculture to river and stream chemical water quality and the ecology. Organic P compounds have received limited attention in past research, due to the agronomic focus on inorganic P and the analytical challenges of quantifying organic P in environmental matrices. Through laboratory and field experiments, this thesis aimed to: (i) characterise organic P within fresh and stored livestock slurry; (ii) quantify organic P export within overland flow and leachate from grasslands, including following livestock slurry application; and (iii) determine the benthic microbial responses to organic P compounds in rivers and streams. Finally, a coupled terrestrial-aquatic modelling approach was developed to quantify the impact of diffuse agricultural P mitigation measures on river water quality. The organic P pool in fresh livestock slurry was substantial and dominated by monoesters, including glycerophosphates, other labile monoesters (e.g. ATP) and inositol-6-phosphates. Storage drove significant changes in the chemical and physical fractionation of P within slurry. Organic P was observed in overland flow and leachate from grassland soil. Significant increases in organic P concentrations within leachate followed slurry application, predominantly in the form of glycerophosphates and inositol-6-phosphates. Within streams, heterotrophic responses to glycerophosphates and inositol-6-phosphate were observed, although these varied depending on background stream P concentrations. However, under certain stream conditions, inhibitory effects of organic P on the autotrophic community were observed. Modelling the efficacy of agricultural P mitigation suggested a best-case scenario in which annual river total P loads decreased by 7.5%, yet this increased to 19.4-25.1% when wastewater effluent was addressed alongside agricultural sources of P. The outcomes of this thesis present an opportunity to develop an organic P focus to the P transfer continuum, alongside highlighting a range of future research priorities related to organic P in the environment

A Study of African Savanna Vegetation Structure, Patterning, and Change

African savannas cover roughly half of the continent, are home to a great diversity of wildlife, and provide ecosystem services to large populations. Savannas showcase a great diversity in vegetation structure, resulting from variation in climatic, edaphic, topographic, and biological factors. Fires play a large role as savannas are the most frequently burned ecosystems on Earth. To study how savanna vegetation structure shifts with environmental factors, it is necessary to gather site data covering the full gradient of climatic and edaphic conditions. Several earlier studies have used coarse resolution satellite remote sensing data to study variation in woody cover. These woody cover estimates have limited accuracy in drylands where the woody component is relatively small, and the data cannot reveal more detailed information on the vegetation structure. We therefore know little about how other structural components, tree densities, crown sizes, and the spatial pattern of woody plants, vary across environmental gradients. This thesis aimed to examine how woody vegetation structure and change in woody cover vary with environmental conditions. The analyses depended on access to very high spatial resolution (\u3c1 \u3em) satellite imagery from sites spread across African savannas. The high resolution data combined with a crown delineation method enabled me to estimate variation in tree densities, mean crown size and the level of aggregation among woody plants. With overlapping older and newer imagery at most of the sites, I was also able to estimate change in woody cover over a 10-year period. I found that higher woody plant aggregation is associated with drier climates, high rainfall variability, and fine-textured soils. These same factors were also indicative of the areas where highly organized periodic vegetation patterns were found. The study also found that observed increases in woody cover across the rainfall gradient is more a result of increasing crown sizes than variation in tree density. The analysis of woody cover change found a mean increase of 0.25 % per year, indicating an ongoing trend of woody encroachment. I could not attribute this trend to any of the investigated environmental factors and it may result from higher atmospheric CO₂ concentrations, which has been proposed in other studies. The most influential predictor of woody cover change in the analysis was the difference between potential woody cover and initial woody cover, which highlights the role of competition for water and density dependent regulation when studying encroachment rates. The second most important predictor was fire frequency. To better understand and explain the dominant ecosystem processes controlling savanna vegetation structure, I constructed a spatially explicit model that simulates the growth of herbaceous and woody vegetation in a landscape. The model reproduced several of the trends in woody vegetation structure earlier found in the remote sensing analysis. These include how tree densities and crowns sizes respond differently to increases in precipitation along the full rainfall range, and the factors controlling the spatial pattern of trees in a landscape

Experimental and computational study of hybrid diffusers for gas turbine combustors

Diffusers are essential in gas turbine combustors, decelerating the compressor efflux prior to the combustion chamber to reduce total pressure losses. Modern, low emission, radially staged combustors require even more diffusion due to the increased flame tube depth of this type of combustor. Furthermore, these high rates of deceleration are accompanied by large adverse pressure gradients and an associated risk of flow separation. Previous studies have shown that hybrid diffusers can achieve high rates of efficient diffusion in far shorter lengths than conventional faired diffusers or dump diffuser systems, representing a potential performance gain and weight saving. Hybrid diffusers consist of a wide angle diffuser immediately downstream of a sudden expansion, with flow separation prevented by bleeding off a small amount of the mainstream flow. However, previous studies have not provided a conclusive understanding of the associated flow mechanisms leading to hybrid diffusers currently being considered high risk. Additionally definitive data does not exist on the influence of bleed gap geometry and therefore hybrid diffusers cannot, currently, be optimised for use in a modern gas turbine. Further issues also not addressed by earlier studies, but concerning the use of hybrid diffuser in gas turbine combustors, are the effect of representative inlet conditions incorporating vane wakes at diffuser inlet, the quality of the bleed air and its potential for use for component cooling, the effect of radial struts within a hybrid diffuser and the quality of the flow delivered to the combustor feed annuli (total pressure losses). Therefore, a predominately experimental study, coupled with CFD predictions, was undertaken to investigate the controlling flow mechanisms of hybrid diffusers and address the questions necessary to evaluate the suitability of hybrid diffusers for use in modern, low emission, radially staged combustion systems. An existing isothermal test facility was used comprising a fully annular, staged combustor downstream of a single stage axial compressor incorporating engine representative outlet guide vanes. Initial experimental work led to rig modifications which allowed a range of hybrid diffusers to be studied. To act as a benchmark the performance of a conventional single-passage, dump diffuser system was first studied. A hybrid diffuser demonstrated a 53% increase in area ratio within the same axial length as the conventional diffuser. Results showed that this hybrid diffuser achieved a 13% increase in static pressure recovery which, in turn, improved the feed to the combustor feed annuli and decreased total pressure loses by 25%. Notably this brought the annulus losses within accepted target values; something the conventional diffuser system was unable to do. Additionally, it was clearly shown, in contradiction to previous studies, that bleeding air via a vortex chamber was not necessary. Bleeding air via a simple duct arrangement achieved the same results without altering the governing flow mechanisms. To provide a better understanding of these flow mechanisms, a computational investigation was also undertaken. A commercial CFD code, Fluent, was used to solve the Reynolds averaged Navier-Stokes equations for an incompressible flow regime, employing a blended second order upwind/central differencing scheme and the SIMPLE pressure correction algorithm. The turbulence was modelled using the k-ε model in conjunction with a standard wall function. Several generic two-dimensional hybrid diffusers were studied in order to reveal the controlling flow mechanisms and enable optimisation of the bleed gap geometry. Importantly, this revealed that many features previously thought to contribute to the flow mechanisms were, in fact, unnecessary. A detailed examination of the flow field, including an analysis of the terms within the momentum equation, demonstrated that the controlling flow mechanisms were not simply a boundary layer bleed but involve a much more complex interaction between the accelerating bleed flow and the diffusing mainstream flow. Firstly, momentum is transferred from the accelerating bleed flow to the diffusing mainstream flow, enabling a fresh boundary layer to be formed on the diffuser wall which is sufficiently energetic to overcome the high rates of diffusion and high adverse pressure gradient. Secondly, the radial pressure gradient created by the bleed causes deflection of the mainstream flow which also transports higher momentum fluid into the boundary layer. Understanding this resulted in a greatly simplified design for the hybrid diffuser not only potentially reducing weight but also reducing bleed flow total pressure losses. Predictions for a three-dimensional representation of the experimental facility displayed many similarities in the flow field and similar performance trends to the experimental data. However, predicted values of total pressure loss and static pressure recovery differed from experimental data and it was thought that this was due to an incomplete description of the turbulence (k and ε) at inlet and/or known problems the k-ε turbulence model has with predicting some unconfined flows. Nonetheless, three-dimensional predictions revealed an interaction between the OGV wake fluid and bleed flow causing localised, but small, modification of the flow mechanisms. Furthermore, it was shown that without the levels of turbulence produced downstream of an axial compressor the hybrid diffuser under study would, in fact, stall. Overall, experimental and computational results obtained in the current research suggest that the performance of hybrid diffusers is more than satisfactory for use within lowemission, staged, gas turbine combustion systems. An understanding of the governing flow mechanisms and the effect of features such as OGV wakes or radial struts has lead to a more practical design of hybrid diffuser, simplifying the geometry and reducing bleed flow total pressure losses (increasing the possibility of this air being used for component cooling)

Investigation of protein-protein interactions: multibody docking, association/dissociation kinetics and macromolecular crowding

Protein-protein interactions are central to understanding how cells carry out their wide array of functions and metabolic procedures. Conventional studies on specific protein interactions focus either on details of one-to-one binding interfaces, or on large networks that require a priori knowledge of binding strengths. Moreover, specific protein interactions, occurring within a crowded macromolecular environment, which is precisely the case for interactions in a real cell, are often under-investigated. A macromolecular simulation package, called BioSimz, has been developed to perform Langevin dynamics simulations on multiple protein-protein interactions at atomic resolution, aimed at bridging the gaps between structural, kinetic and crowding studies on protein-protein interactions. Simulations on twenty-seven experimentally determined protein-protein interactions, indicated that the use of contact frequency information of proteins forming specific encounters can guide docking algorithms towards the most likely binding regions. Further evidence from eleven benchmarked protein interactions showed that the association rate constant of a complex, kon, can be estimated, with good agreement to experimental values, based on the retention time of its specific encounter. Performing these simulations with ten types of environmental protein crowders, it suggests, from the change of kon, that macromolecular crowding improves the association kinetics of slower-binding proteins, while it damps the association kinetics of fast, electrostatics-driven protein-protein interactions. It is hypothesised, based on evidence from docking, kinetics and crowding, that the dynamics of specific protein-protein encounters is vitally important in determining their association affinity. There are multiple factors by which encounter dynamics, and subsequently the kon, can be influenced, such as anchor residues, long-range forces, and environmental steering via crowders’ electrostatics and/or volume exclusion. The capacity of emulating these conditions on a common platform not only provides a holistic view of interacting dynamics, but also offers the possibility of evaluating and engineering protein-protein interactions from aspects that have never been opened before